ABSTRACT A large number of studies require sampling biological signals, stimulating the brain, or infusing test substances in freely moving mice. Although several forms of tethers are currently available for this purpose, these devices restrain the mice?s activity to some degree. The animal?s mobility is usually reduced even more when several connections are needed with the mouse (i.e., electroencephalogram (EEG)/electromyogram (EMG) wires, fiber optics, and infusion lines). Telemetric devices and miniature pumps avoid the tethers, but they still restrict the animal?s movement because they are very heavy for a mouse (i.e., smallest telemetry EEG/EMG transmitter weighs ~4 grams or ~20% of the mouse?s body weight). It is expected that restraining the mouse?s movement will negatively influence the results of the study because it would cause stress and change various physiological parameters in the mouse. We recently developed a system with optical, electrical, and fluid connections that can be used for mice or any other small animal that does not require the use of a commutator, swivel, or fiber optic rotary joint. The specific aim of this application is to modify our system for the use in studies involving connections of infusion lines with freely moving mice. Such connections are commonly used in a large number of research studies (drug infusion, microdialysis, monitoring of blood pressure, etc.). Therefore, the new modification will significantly increase the capability and commercial potential of this system. Additionally, we will adapt our system for the use in SmartCageTM, thus creating a powerful platform for drug discovery studies. It will allow for completing the research projects faster and with a lower cost.